Structure-guided optimization of small molecule c-Abl activators

@inproceedings{Hong2014StructureguidedOO,
title={Structure-guided optimization of small molecule c-Abl activators},
author={Xuan Hong and Ping Cao and Yoshiaki Washio and Graham Simpson and Nino Campobasso and Jingsong Yang and Jennifer Borthwick and George Burton and Julien Chabanet and Sophie Bertrand and Helen Evans and Robert J. Young and Junya Qu and Hu Li and Josh Cottom and Paris Ward and Hong Zhang and Thau Ho and Donghui Qin and Siegfried Christensen and Martha S. Head},
booktitle={Journal of Computer-Aided Molecular Design},
year={2014}
}

c-Abl kinase is maintained in its normal inactive state in the cell through an assembled, compact conformation. We describe two chemical series that bind to the myristoyl site of the c-Abl kinase domain and stimulate c-Abl activation. We hypothesize that these molecules activate c-Abl either by blocking the C-terminal helix from adopting a bent conformation that is critical for the formation of the autoinhibited conformation or by simply providing no stabilizing interactions to the bent… CONTINUE READING